Safety of and Immune Response to DEN4 Vaccine Component Candidate for Dengue Virus
Infection with dengue viruses is one of the leading causes of hospitalization and death in children in several tropical Asian counties. The World Health Organization (WHO) estimates that these viruses are responsible for more than 50 million cases of dengue fever (DF) and approximately 0.5 million cases of the more severe disease, dengue hemorrhagic fever/ shock syndrome (DHF/DSS) annually. Because dengue viruses are endemic in most tropical and subtropical regions, keeping more than 2 billion persons at risk for acquiring dengue, the WHO has made development of a dengue vaccine a top priority.
The purpose of this study is to evaluate the safety and effectiveness of a candidate DEN4 vaccine aimed at preventing infection with dengue virus serotype 4.
Dengue Shock Syndrome
Dengue Hemorrhagic Fever
Biological: DEN4 Vaccine Candidate
Biological: DEN4 Vaccine Placebo
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
|Official Title:||Phase I Evaluation of the Safety and Immunogenicity of rDEN4delta30 Lot# 109A, a Live Attenuated DEN4 Vaccine, in Healthy Flavivirus-naïve Adult Volunteers.|
- Immunogenicity of vaccine candidate, as assessed by neutralizing antibody titers to DEN4 [ Time Frame: At Weeks 4 and 6 following vaccination ] [ Designated as safety issue: No ]
- Safety of vaccine candidate, as assessed by the frequency of vaccine-related adverse events, graded by severity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Frequency, quantity, and duration of viremia following vaccination [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Number of vaccinees infected with vaccine virus [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Infectivity rates, safety, and immunogenicity of a single dose of candidate vaccine compared with previous rates from a previous lot of similar vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Durability of antibody response [ Time Frame: At 26 Weeks following vaccination ] [ Designated as safety issue: No ]
- Phenotype of peripheral blood mononuclear cells at primary infection with the rDEN4delta30 vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Cellular immune response to primary infection with the rDEN4delta30 vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
|Study Start Date:||July 2009|
|Study Completion Date:||May 2010|
|Primary Completion Date:||May 2010 (Final data collection date for primary outcome measure)|
Participants will receive a single immunization for Dengue virus serotype 4 (DEN4)
Biological: DEN4 Vaccine Candidate
DEN4 Vaccine Candidate
Participants will receive a single immunization on Study Day 0. Vaccine will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL.
Placebo Comparator: 2
Participants will receive a single immunization in the form of placebo resembling vaccine for DEN 4
Biological: DEN4 Vaccine Placebo
DEN4 Vaccine Placebo
Participants will receive a single immunization on Study Day 0. Placebo will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL.
Dengue viruses are endemic in most tropical and subtropical regions of the world with more than 2 billion persons at risk for acquiring dengue. There are four serotypes of dengue virus (DEN 1, DEN 2, DEN 3, and DEN 4) each capable of causing dengue illness ranging from mild, self-limited febrile illness to life-threatening disease. Because previous infection with one dengue serotype can increase the risk for DHF/DSS following infection with a different serotype, immunization would ideally provide immunity against all four dengue viral serotypes.
Several live, attenuated dengue vaccines have been tested in Phase I and/or Phase II clinical trials. Although some have appeared promising in early trials, none have been able to meet the requirements for a safe and effective vaccine. Meeting these requirements has been particularly difficult when testing vaccines containing all four serotypes. The vaccine candidate in this study is live-attenuated rDEN4delta30, which will target the DEN4 serotype, it is a potential component for a future tetravalent dengue vaccine.
This is a double-blind, random assignment, placebo-controlled study in healthy, adult volunteers. The purpose of this study is to evaluate the safety and effectiveness of a single dose of DEN4 vaccine. Some participants will be receiving placebo as a comparative measure, to better assess vaccine-associated versus non vaccine-associated adverse events.
To qualify for participation in the study, volunteers will undergo an eligibility screening which will include medical history, physical exam, hematology testing, liver and renal function testing, coagulation studies, human immunodeficiency virus (HIV) and hepatitis B and C screening, urinalysis, and screening for pervious flavivirus infection. Urine pregnancy testing will also be required for female volunteers.
Duration of individual participation in the study is approximately 26 weeks following vaccination on Study Day 0. Volunteers will be randomly assigned to receive either rDEN4delta30 or placebo; 50 participants will receive the vaccine, 20 will receive placebo. On the day of vaccination, all volunteers will be reassessed by study personnel to ensure continued eligibility, vital signs will be taken, and a physical exam will be performed. Female participants will also have a pregnancy test and review of acceptable pregnancy prevention methods. Eligible participants will receive a vaccination of Study Day 0, followed by a 30 minute post vaccination assessment for adverse events. After vaccination, volunteers will be evaluated in the clinic approximately every other day for the first 16 days if study.
During the course of study, volunteers will have blood drawn and clinical evaluations performed on Study Days 21, 28, 42, and 180 post-vaccination. All participants will be asked to record oral temperatures 3 times a day for the first 16 days post-vaccination.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00919178
|United States, Maryland|
|Center for Immunization Research, Johns Hopkins School of Public Health|
|Baltimore, Maryland, United States|
|United States, Vermont|
|University of Vermont Vaccine Testing Center|
|Burlington, Vermont, United States|
|Principal Investigator:||Anna Durbin, MD||Johns Hopkins School of Public Health|
|Principal Investigator:||Beth Kirkpatrick, MD||University of Vermont Vaccine Testing Center|